The objective of this study is to demonstrate the safety and efficacy of tipranavir/ritonavir versus an active control arm in highly treatment experienced Human immunodeficiency virus-1 infected patients. Patients must have a viral load > =1000 cells/mL, and genotype indicating at least one resistance conferring protease inhibitor-mutation as determined from a predefined panel of mutations. Any CD4+ count is acceptable.

Time to Treatment Failure Through 48 Weeks of Treatment [ Time Frame: after 48 weeks of treatment ] [ Designated as safety issue: No ]

Time to treatment failure is defined as 0 for patients who never achieve TR otherwise time to treatment failure is the earliest time of death, discontinuation of the study drug or introduction of a new anti-retroviral drug to the regimen if it is not solely related to either toxicity or intolerance clearly attributable to a background, or the first of two consecutive visits with Log(baseline Viral Load) - Log(on-treatment Viral Load) < 1.

Time to Treatment Failure Through 96 Weeks of Treatment [ Time Frame: after 96 weeks of treatment ] [ Designated as safety issue: No ]

Time to treatment failure is defined as 0 for patients who never achieve TR otherwise time to treatment failure is the earliest time of death, discontinuation of the study drug or introduction of a new anti-retroviral drug to the regimen if it is not solely related to either toxicity or intolerance clearly attributable to a background, or the first of two consecutive visits with Log(baseline Viral Load) - Log(on-treatment Viral Load) < 1.

Time to Confirmed Virologic Failure Through 48 Weeks of Treatment [ Time Frame: after 48 weeks of treatment ] [ Designated as safety issue: No ]

Time to virologic failure is defined as the time from the start of treatment to the last measurement where the Log(baseline viral load)-Log(on-treatment viral load)>1 before a 2 consecutive measurements where Log(baseline viral load)-Log(on-treatment viral load)<1.

Time to Confirmed Virologic Failure Through 96 Weeks of Treatment [ Time Frame: after 96 weeks of treatment ] [ Designated as safety issue: No ]

Time to virologic failure is defined as the time from the start of treatment to the last measurement where the Log(baseline viral load)-Log(on-treatment viral load)>1 before a 2 consecutive measurements where Log(baseline viral load)-Log(on-treatment viral load)<1.

Virologic Response [ Time Frame: Week 2 through Week 96 (at any point during trial) ] [ Designated as safety issue: No ]

Screening genotypic resistance report indicating both of the following:

at least one primary protease mutation at the following sites 30N, 46I/L, 48V, 50V, 82A/F/L/T, 84V or 90M , and

no more than two protease mutations on codons 33, 82, 84, or 90.

At least 3 consecutive months experience taking antiretrovirals from each of the classes of Nucleoside reverse transcriptase inhibitor(s), Non-nucleoside reverse transcriptase inhibitor(s), and Protease inhibitor(s) at some point in treatment history,

with at least 2 Protease inhibitor-based regimens (minimum 3 months of exposure of each), one of which must be part of the current regimen, and

Acceptable medical history, as assessed by the investigator, with chest X-ray and electrocardiogram within 1 year of study participation.

Willingness to abstain from ingesting substances during the study which may alter plasma study drug levels by interaction with the cytochrome P450 system.

A prior Acquired immune deficiency syndrome-defining event is acceptable as long as it has resolved or the patient has been on stable treatment for at least 2 months (Acquired immune deficiency syndrome related complex is acceptable).

Exclusion Criteria:

Antiretroviral medication naïve.

Patients on recent drug holiday, defined as off antiretroviral medications for at least 7 consecutive days within the last 3 months.

have a positive serum pregnancy test at screening or during the study,

are breast feeding

are planning to become pregnant, or

are not willing to use a barrier method of contraception, or

require ethinyl estradiol administration

Prior tipranavir use.

Use of investigational medications within 30 days before study entry or during the trial. (T-20 [enfuvirtide] and Tenofovir (Viread), investigational at the time of writing of this protocol, will be allowed.)

Use of immunomodulatory drugs within 30 days before study entry or during the trial (e.g. interferon, cyclosporin, hydroxyurea, interleukin 2).

Inability to adhere to the requirements of the protocol, including active substance abuse as assessed by the investigator.

In the opinion of the investigator, likely survival of less than 12 months because of underlying disease.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00144170